Chronic hepatocellular damage results in the development of liver fibrosis and subsequently liver cirrhosis. Liver fibrosis is the scarring process, in which extracellular matrix proteins, including collagens, accumulate in the liver for damage repair. Liver cirrhosis involves regeneration of nodules surrounded by fibrous bands. It is an advanced stage of liver fibrosis accompanied with distortion of the hepatic vasculature. While a number of therapeutic approaches for delaying the progression of liver cirrhosis or even reverse cirrhosis are currently being developed, liver transplantation remains the only curative option for treating live cirrhosis. Bataller et al., J Clin Invest, 2005, 115(2):209-18; and Schuppan et al., Lancet. 2008 371(9615):838-51.
Interleukin IL-20 (IL-20) is a member of the IL-10 family, which includes IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26. Blumberg, et al., 2001, Cell 104:9-19; Pestka et al., 2004, Annu Rev Immunol 22:929-979. IL-20 is expressed in monocytes, epithelial cells, and endothelial cells and acts on multiple cell types by activating a heterodimer receptor complex of either IL-20R1/IL-20R2 or IL-22R1/IL-20R2. Dumoutier, et al., 2001, J Immunol 167:3545-3549). IL-20 was found to be involved in various inflammatory diseases, such as psoriasis (Blumberg et al., 2001; Sa et al., 2007, J Immunol 178:2229-2240; and Wei et al., 2005, Clin Immunol 117:65-72), rheumatoid arthritis (Hsu, et al., 2006, Arthritis Rheum 54:2722-2733), atherosclerosis (Caligiuri, et al. 2006, Arterioscler Thromb Vasc Biol 26:1929-1930; and Chen et al., 2006, Arterioscler Thromb Vasc Biol 26:2090-2095), ischemic stroke (Chen et al., 2009, J Immunol 182:5003-5012), and renal failure (Li et al., 2008, Genes Immun 9:395-404). See also Wei et al., 2006, J Biomed Sci 13:601-612.